The effect of CaO/Al2O3 (=C/A) ratio of the ladle slag on the formation behavior of non-metallic inclusions in the Mn-V-alloyed steel was investigated using both the experimental method and refractory-slag-metal-inclusion (ReSMI) multiphase reactions simulation. The formation behavior of inclusion was strongly affected by the activity of MgO in the initial slag at the early stage of the reaction. However, since the MgO activity converged to unity due to MgO dissolution from refractory to slag during the reaction, the formation behavior of inclusion was affected by the activity of CaO and Al2O3 in the slag rather than that of MgO at the final stage of the reaction. From the experimental results and ReSMI multiphase reaction model, the formation behavior of inclusions could be divided into three cases according to the C/A ratio of the slag as follows; 1) C/A < 1.5; Alumina → Spinel → Spinel + Liquid oxide, 2) 1.5 < C/A < 2.5; Alumina → Spinel → Liquid oxide, 3) C/A > 3.0; Alumina → Spinel → Liquid oxide → Magnesia. Therefore, it was concluded that the C/A ratio of the ladle slag should be controlled from about 1.5 to 2.5 in order to suppress the harmful solid inclusions such as spinel during secondary refining processes.